The primary objectives of this study are to evaluate the safety and reactogenicity of mRNA-1010, and to evaluate relative vaccine efficacy (rVE) of mRNA-1010 versus an active comparator against reverse transcription polymerase chain reaction (RT-PCR)-confirmed protocol-defined influenza-like illness (ILI) caused by any influenza A or B strains.

Inclusion Criteria:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

• Participants who are assigned female at birth or can become pregnant are eligible to participate if:

  • The participant is a person of nonchildbearing potential (PONCBP) or
  • The participant is a person of childbearing potential (POCBP) who:

• Is not breast/chest feeding.

• Is using an acceptable contraceptive method at least 28 days prior to Day 1 (Baseline) to at least 90 days after Day 1 (Baseline).

• Has a negative highly sensitive pregnancy test (urine or serum as required by local regulation or institutional review board [IRB]/independent ethics committee [IEC]) at the Screening Visit and before study intervention (if the Day 1 [Baseline] Visit is not on the same day as the Screening Visit).

Exclusion Criteria:

• Acutely ill or febrile (temperature ≥38.0 degrees Celsius (℃) [100.4° Fahrenheit [F]]) within 72 hours prior to Day 1 (Baseline).
• Close contact with someone with laboratory-confirmed influenza infection or with someone who has been treated with antiviral therapies for influenza (for example, Tamiflu®/oseltamivir) within 5 days prior to Day 1 (Baseline).
• History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of study endpoints, assessment of immune response, or adherence to study procedures.
• Reported history of congenital or acquired immunodeficiency, immunosuppressive condition, asplenia, or recurrent severe infections disease.
• Tested positive for influenza by local health authority-approved testing methods within 180 days prior to Day 1 (Baseline).
• History of anaphylaxis or severe hypersensitivity reaction requiring medical intervention after receipt of any of the following: mRNA vaccine or therapeutic; components of an mRNA vaccine or therapeutic; influenza vaccine; or components of an influenza vaccine, including egg protein.
• Malignancy within 2 years prior to Day 1 (Baseline) (adequately treated basal cell carcinoma and squamous cell carcinoma are allowed).
• Received corticosteroids at ≥10 milligram (mg)/day of prednisone or equivalent for >14 days in total within 90 days prior to Day 1 (Baseline) or is anticipating the need for corticosteroids at any time during the study.
• Received systemic immunosuppressive treatment, including long-acting biological therapies that affect immune responses (for example, infliximab), within 180 days prior to Day 1 (Baseline) or plans to do so during the study.
• Treated with antiviral therapies for influenza (for example, Tamiflu) within 180 days prior to Day 1 (Baseline).
• Received any vaccine authorized or approved by local health agency within 28 days prior to Day 1 (Baseline) or plans to do so within 14 days after Day 1 (Baseline).
• Received a licensed seasonal influenza vaccine within 180 days prior to Day 1 (Baseline) or plans to do so (outside of this study) at any time during the study.
• Received an investigational seasonal influenza vaccine within 1 year prior to Day 1 (Baseline). Note: participants from mRNA-1010-P304 Season 1 are NOT eligible to re enroll into Season 2.
• Participated in a clinical study with investigational treatment within 90 days prior to Day 1 (Baseline) based on the medical history interview or plans to do so while participating in this study.
• Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study staff, or Sponsor personnel.